1. Field of the Invention
The present invention relates to devices for membrane separation of a separable component from a liquid sample. More particularly, this invention relates to self-contained devices for separation of the liquid component from the cellular component of a blood sample without the use of a centrifuge, an auxiliary circulating system, an auxiliary pump or the like and a method for using these devices.
2. Description of the Prior Art
A common method of obtaining a blood sample involves the use of a two-cannula needle assembly and an evacuated glass tube having a pierceable stopper. The method involves inserting one cannula of the needle assembly into the subject's vein and piercing the stopper of the evacuated glass tube with the other cannula of the needle assembly, thereby establishing fluid communication between the vein and the interior of the glass tube. Due to the lower pressures within the evacuated glass tube blood is drawn from the subject into the tube. Evacuated tubes and needle assemblies for use therewith are described in U.S. Pat. No. 3,469,572 to Nehring. Such devices are commercially available under the VACUTAINER Brand name from Becton, Dickinson and Company, Franklin Lakes, N.J.
The blood sample, in the evacuated glass tube, may then be placed in a centrifuge and centrifuged until the more dense cellular component of the blood sample is driven to the bottom of the tube and the less dense plasma is positioned at the top of the sample. The stopper from the tube may then be removed and the plasma sample poured off for subsequent testing. If serum is desired the blood sample is allowed to clot before centrifuging the blood sample.
U.S. Pat. No. 4,057,499 to Buono teaches the collection of a plasma or serum sample using a sampling member having a hollow interior for the collection of liquid and a piston connected to one end of the sampling member. The piston includes a lip for forming a seal with the interior walls of the sample containing glass tube and an interior portion contains a filter and a one-way valve. In use, a blood sample, in a glass tube, is centrifuged to separate the liquid and the cellular phases and then the device of Buono is placed in the tube and forced along the inner tube surface so that the piston passes through the liquid portion of the sample forcing the liquid portion through the filter and through the valve into the hollow interior of the device. The device containing a portion of the liquid sample is then removed from the glass tube. Buono teaches that it is desirable to physically separate the liquid phase of the sample from the cellular phase to prevent deleterious chemical interaction between the two. Accordingly, Buono teaches the use of a centrifuge and a separate filtering apparatus to obtain the plasma or serum sample.
It is known that forcing a blood sample through a filter membrane is not a practical method of separating the liquid and the cellular components because the filter membrane would soon become caked with the cellular components and unable to perform its task as a filter. Accordingly, it is believed that if the liquid phase of the blood sample is to be filtered from the cellular portion of the blood sample, without the use of a centrifuge, a cross- flow filter arrangement should be provided. In a cross-flow arrangement, the blood sample flows across the surface of the filter membrane in a direction parallel to the major axis of the membrane while a secondary force provides a pressure differential between the blood side of the membrane and the liquid side so that the liquid phase will pass through the membrane. U.S. Pat. Nos. 3,211,645; 4,191,182; 4,212,742 and 4,343,705 teach various devices for the filtration of liquid using a cross-flow technique. In each of these patents, the devices utilized require an applied pressure driving force from a separate source across the membrane filter in order to bring about the proper separation. That is, a separate pumping and/or circulating device must be used in conjunction with the cross-flow filter.
It is believed that the cross-flow method of filtration is superior because when the blood sample is caused to flow in parallel relationship across the filter membrane there is less tendency for the membrane to be clogged by the cellular portion of the blood sample and therefore allowing the blood to be filtered without the use of a centrifuge. In any event, all of the devices and methods described hereinabove require the use of relatively expensive support devices such as a centrifuge, liquid pumping and/or circulating systems, or the like. In addition, dependency on additional equipment can consume valuable time in emergency situations wherein the liquid phase of the patient's blood sample must be analyzed properly in order to diagnose the problem and/or to provide proper emergency treatment. In these situations, it is desirable to provide a device for the separation of the liquid phase of the blood sample from the cellular phase immediately upon the drawing of the blood sample without further steps.
U.S. Pat. No. 3,705,100 to Blatt et al. teaches a device for separating plasma from whole blood, without the use of a centrifuge or recirculating pumps, which involves drawing a blood sample from the patient, apparently using a hypodermic syringe. After the blood is drawn, the needle or other apparatus is removed from the syringe and the syringe is connected to a filter housing and spring means which provides positive pressure to the contents of the syringe through the syringe plunger. Blood is driven through the syringe tip around a circular pathway and out into the environment where it is collected in an open container while plasma passes through the filter medium and drips into a second reservoir. While the teachings of Blatt et al. provide for plasma separation without the use of a centrifuge or separate pumping and/or circulating devices it still has deficiencies in that it requires multiple handling steps with respect to the blood sample exposing the person taking the sample with potential for being contaminated by the blood sample. In addition, the sample can be exposed to the environment during the procedure using the Blatt et al. device thereby possibly compromising any laboratory results at any laboratory analysis of the plasma obtained therefrom.
Incorporated by reference is the patent application of Oberhardt et al. presently assigned to the assignee hereof (Ser. No. 694,717 and filed on Jan. 25, 1985) which teaches an improved device for the separation of the lighter fraction from the heavier fraction of a liquid sample which operates without the use of additional equipment such as centrifuges and pumps to produce an isolated quantity of the lighter fraction of the liquid. The device of Oberhardt et al. avoids the multiple steps and exposure to the environment of the device taught by Blatt et al. Oberhardt et al. teach a device for separating plasma from blood separating the lighter fraction from the heavier fraction of a liquid sample for use with two evacuated receptacles having a housing with an interior cavity and a membrane separator dividing the interior cavity into a first portion and a second portion. Inlet means is provided for fluid communication between the first portion of the cavity and the source of the liquid sample and first communication means is provided for communication between the first portion of the cavity and an evacuated receptacle. A second communication means is provided for fluid communication between the second portion of the interior cavity and a second evacuated receptacle. When used with blood, the device of Oberhardt et al. can be connected directly to the patient wherein the first and second evacuated tubes are placed in fluid communication with the first and second communication means so that the blood flow sample flows through the inlet means along the separator membrane through the first communication means and into the first evacuated receptacle, simultaneously, plasma is drawn through the membrane and the second communication means and into the second evacuated receptacle. The device of Oberhardt et al. overcomes the deficiency of the prior art devices while allowing a blood sample to be taken directly from the patient and into evacuated receptacles without being exposed to the environment. Oberhardt et al. also teach a method using the device described hereinabove comprising the steps of withdrawing blood from the patient across the surface of the separator membrane and simultaneously drawing plasma from the blood through the membrane while the blood is being withdrawn from the patient.
The device of Oberhardt et al. is a substantial improvement over the prior art blood separation devices. However, it requires the use of two evacuated receptacles and depending on the porosity of the separation membrane and the structure of the communication means for connecting the interior of the housing with the evacuated receptacle it may be necessary to coordinate the fluid communication between the two receptacles so that they are connected, for example, simultaneously to avoid vacuum loss through the unconnected fluid communication means in the housing.
The prior art teaches devices and methods for separating the liquid phase from the cellular phase of a blood sample while it is being drawn from the patient using two separate evacuated receptacles. There is still a need for a simple, straight- forward, reliable, easily fabricated device for the membrane separation of the components of a liquid sample, for example, separating a non-particulate phase from a particulate phase of a liquid, or separating plasma from blood as it is being withdrawn from the patient wherein the system will operate with a single evacuated receptacle to reduce the complexity of the system and to eliminate the need for specialty apparatus or procedural complexity involved with timing of the activation of multiple evacuated tubes with the device.